In 15-20% of migraineurs, headaches are preceded by a visual illusion known as an aura. Typically, the aura appears as a serrated arc of scintillating crenellated shapes that moves within one visual field, from the center to the periphery, over a period of 5-40 minutes. In some cases, the aura is accompanied by significant morbidity (persistent scotoma) or infrequently, cortical infarcts in the unusual territory of the posterior cerebral artery. This research application proposes four aims designed to clarify the neurophysiological, metabolic and hemodynamic basis of the migraine aura, and to extend preliminary data from naturally-triggered migraineurs, suggesting that visual aura is characterized by propagation of a BOLD signal change similar to cortical spreading depression in animal models. The proposed experiments will use a range of imaging techniques, electrophysiology, diffusion weighted imaging, and analysis tools such as cortical flattening and retinotopic mapping. Specific Aim 1 will examine metabolic and neuronal changes occurring during the initial and the later part of naturally-triggered and spontaneous aura. It will test whether a neuronal depolarization is the leading event in migraine aura, by measuring blood flow, cerebral rate of oxygen utilization, water diffusion, and cerebral blood volume, along with neurophysiological signals (EEG). Specific aim 2 will use advanced fMRI techniques to reveal the point source of the aura representation in visual cortex. We will also track the correspondence between the visual percept and the retinotopic representation of the time course of the aura, to test the hypothesis that the visual aura correlates with a spreading BOLD signal change. Specific Aim 3 will test whether the migraine aura exhibits the same characteristics (e.g. spreading hemodynamic and metabolic signal change) in non-visual cortex, using the same approaches in somatosensory cortex as those used to study visual aura. Taken together, these aims are intended to provide additional insight into the pathophysiology of migraine aura and a basis for the identify of novel targets.